Halozyme Corp. CEO Helen Torley told BioWorld that she expects the latest news about the firm's subcutaneous (subcu) hyaluronidase technology "on the heels of the Rituxan Hycela approval in June of this year by the FDA [will] spark even more rapid growth of companies wanting to sign an Enhanze deal."

Six partners in hand already, San Diego-based Halozyme broke ground with a new arrangement involving Bristol-Myers Squibb Co. (BMS), of New York: a global collaboration and license agreement to develop BMS immuno-oncology (I-O) medicines using Halozyme's Enhanze drug delivery approach, based on the recombinant human hyaluronidase enzyme, or rHuPH20. Using the compound can let drugs ordinarily given by the intravenous route be used subcu and, for those already given subcu, reduce the need for multiple injections.

Under the terms of the BMS arrangement, Halozyme will collect $105 million for access to Enhanze. BMS has designated multiple I-O targets, including PD-1, and owns an option to select up to 11 more targets within five years. Halozyme stands to earn milestone payments of up to $160 million for each target, and more for combo products, subject to achievement of specified development, regulatory and sales-based goals. If drugs are commercialized, BMS will pay royalties, too.

"They have selected some other targets, not named as yet," Torley said. "That's not uncommon in our deals," with partners holding back information for competitive reasons.

Also, Halozyme is expanding a 2006 pact with Roche Holding AG, of Basel, Switzerland, which has agreed to license Enhanze for exclusive development of an undisclosed therapeutic target. Halozyme gets $30 million right away, with the chance to bank up to $160 million more if specified bells ring in the development, regulatory and sales areas. Included are tiered, mid-single-digit royalties.

Halozyme's first tie-up with Roche led to the pharma giant developing a pair of subcu formulations of cancer drugs for markets worldwide. More recently folded into the contract was the study of Halozyme's oncology drug, PEGPH-20 (a pegylated version of the same approach deployed by Enhanze), with Roche's Tecentriq (atezolizumab); a clinical collaboration started last year. Tecentriq is indicated for advanced urothelial carcinoma and in patients with metastatic non-small-cell lung cancer (NSCLC).

"Roche has selected all of the targets in that original agreement," Torley said, adding that the Swiss firm was "the company that helped us get where we are today with the success they've had with Rituxan [rituximab] and Herceptin [trastuzumab]."

The PEGPH-20 clinical collaboration will include the study of eight cancers in combo with Tecentriq, she said.

In June, the FDA cleared Roche's Rituxan Hycela (rituximab and hyaluronidase human) as a subcu injection for the treatment of adults with previously untreated and relapsed or refractory follicular lymphoma, previously untreated diffuse large B-cell lymphoma, and previously untreated as well as previously treated chronic lymphocytic leukemia. The new therapy includes the same monoclonal antibody as intravenous Rituxan in combination with hyaluronidase, thereby reducing administration time from 1.5 hours or longer to five to seven minutes.

Hycela involves a 10 mL to 15 mL injection, "but we also are used in a technology for Shire that's called Hyqvia, where patients can receive up to 300 mL in a subcu injection over an hour to get their entire month's dose of immune globulin," Torley said.

Halozyme's success has to do with "an increased recognition of two dynamics going on," she said. "Patients are living longer and better lives with great new therapies. What's holding them back is often the need to go back to an infusion center and spend half a day there. Sometimes the infusion centers are busy, and they actually get home without being treated. We're hearing there are examples of that."

Revenue projections doubled

Once a deal is signed, Halozyme serves mainly as an advisor to the company, "from the point of view of regulatory strategy and technical aspects of how to co-formulate the molecules," Torley said. Her firm makes the active pharmaceutical ingredient (API) and the rest is done by the partner, "with us meeting with them on a regular basis to offer advice. It isn't of high-resource intensity for us, except for the manufacture of the API."

Halozyme was "founded on the basis of attacking hyaluronan," substrate of hyaluronidase, Torley said. The two-sugar polymer is found throughout the body but "particularly under the skin," where it forms "a gel-like barrier" that prevents injecting large amounts of liquid. Enhanze technology temporarily degrades hyaluronan – a culprit that also accumulates around certain cancer cells and can impede the action of chemotherapy.

Enter PEGPH-20. In January, Halozyme reported top-line results from the combined analysis of stages 1 and 2 and stage 2 alone of its HALO-202 study as of December of last year. HALO-202 is a phase II, randomized, multicenter trial of lead investigational drug PEGPH-20 in combination with Abraxane (nab-paclitaxel, Celgene Corp.) and gemcitabine in stage IV pancreas cancer patients. Among the findings, the primary endpoints were achieved, showing a statistically significant increase in progression-free survival (PFS) for the efficacy evaluable population and by demonstrating a reduction in the rate of thromboembolic events in stage 2 of the study in the PEGPH-20 arm. The results were discussed at the American Society of Clinical Oncology meeting in Chicago this year, and a phase III trial is underway with PFS and overall survival as the two primary endpoints.

Phase Ib studies are ongoing with PEGPH-20 in NSCLC and gastric cancer in combination with Keytruda (pembrolizumab, Merck & Co. Inc.), as well as in breast cancer when paired with Halaven (eribulin, Eisai Inc.).

Torley said she wants Halozyme to become the "go-to" company for subcu formulations. The class of monoclonal antibodies is where Enhanze is "mostly being used to date, in all sorts of disease areas, even outside of oncology," but "we see many molecules out there in leading companies" that could benefit across drug types, and the firm is "in active discussions with a number" of them, she said.

"We're feeling very good about our current situation" financially, Torley said, noting that the most recent deals have doubled Halozyme's revenue projections for this year while leaving expense guidance unchanged. The firm is "moving into a positive cash flow situation," she said. "We estimate year-end having $380 million to $395 million in cash. That's a very healthy balance for the company to get our work done."

Shares of Halozyme (NASDAQ:HALO) closed Thursday at 15.98, up $2.80, or 21.2 percent.